Ligand binding histidine

B. and Willson, T.M. (2003) X-ray crystal structure of the liver X receptor (> ligand binding domain regulation by a histidine-tryptophan switch. The Journal of Biological Chemistry, 278, 27138-27143. 

Studies on the effect of pH on peroxidase catalysis, or the heme-linked ionization, have provided much information on peroxidase catalysis and the active site structure. Heme-linked ionization has been observed in kinetic, electrochemical, absorption spectroscopic, proton balance, and Raman spectroscopic studies. Kinetic studies show that compound I formation is base-catalyzed (72). The pKa values are in the range of 3 to 6. The reactions of compounds I and II with substrates are also pH-dependent with pKa values in a similar range (72). Ligand binding (e.g. CO, O2 or halide ions) to ferrous and ferric peroxidases is also pH-dependent. A wide range of pKa values has been reported (72). The redox potentials of Fe3+/Fe2+ couples for peroxidases measured so far are all affected by pH. The pKa values are between 6 and 8, indicative of an imidazole group of a histidine residue (6, 31-33),... 

The bacterial chemoreceptor (Figs. 11-8 and 19-5) has a very small ligand-binding domain and a larger internal domain that activates a histidine kinase. Many growth-factor receptors, including the insulin receptor (Figs. 11-11,11-12), have internal domains with protein tyrosine kinase activity. 

Reactions of isolated FeMoco have also been used in attempts to identify substrate binding sites. Interpretation of these studies is complicated by the existence of vacant protein ligand binding sites on FeMoco, i.e., the sites where cysteine and histidine bind FeMoco to the protein. It is assumed that in extracted cofactor these sites are occupied by the solvent iV-methylformamide. 19F NMR and x-ray absorption experiments [82] and EPR data [83] have demonstrated that CN and methylisocyanide bind to isolated FeMoco. The EPR data indicated that there may be more than one site for CN binding but that one of these may be the tetrahedral iron atom that binds cysteine in the protein. 

The most notable difference between the acid and basic forms of the PBP is the conformation of the C-terminus. In the basic form the C-terminus is extended, on the surface of the protein (Sandler et al., 2000), while in the acid form the C-terminus forms a seventh a-helix, which occupies the pheromonebinding cavity. The loop with two vicinal histidine residues (69 and 70) has also moved significantly between the two forms, suggesting that titration of one of these residues has a profound effect on the conformation of the PBP (Horst et al., 2001). Consistent with this, mutation of histidines 69 and 70 to alanine, abolished a conformational change detectable upon ligand binding (Mohl et al., 2002). 

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